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Co-culture with MSC-derived BM-adipocytes inhibits spontaneous apoptosis of primary AMoL cells (S1); Co-culture with BM adipocytes activates p38MAPK cascade and protein folding in AMoL cells (S2); Network of proteins involved in the effects of BM-adipocyte co-culture in U937 cells (S3).

Leukemia cells in the bone marrow must meet the biochemical demands of increased cell proliferation and also survive by continually adapting to fluctuations in nutrient and oxygen availability. Thus, targeting metabolic abnormalities in leukemia cells located in the bone marrow is a novel therapeutic approach. In this study, we investigated the metabolic role of bone marrow adipocytes in supporting the growth of leukemic blasts. Prevention of nutrient starvation–induced apoptosis of leukemic cells by bone marrow adipocytes, as well as the metabolic and molecular mechanisms involved in this process, was investigated using various analytic techniques. In acute monocytic leukemia (AMoL) cells, the prevention of spontaneous apoptosis by bone marrow adipocytes was associated with an increase in fatty acid β-oxidation (FAO) along with the upregulation of PPARγ, FABP4, CD36, and BCL2 genes. In AMoL cells, bone marrow adipocyte coculture increased adiponectin receptor gene expression and its downstream target stress response kinase AMPK, p38 MAPK with autophagy activation, and upregulated antiapoptotic chaperone HSPs. Inhibition of FAO disrupted metabolic homeostasis, increased reactive oxygen species production, and induced the integrated stress response mediator ATF4 and apoptosis in AMoL cells cocultured with bone marrow adipocytes. Our results suggest that bone marrow adipocytes support AMoL cell survival by regulating their metabolic energy balance and that the disruption of FAO in bone marrow adipocytes may be an alternative, novel therapeutic strategy for AMoL therapy. Cancer Res; 77(6); 1453–64. ©2017 AACR.

Clinical characteristics of AMoL patients (S1); Quantitative expression of metabolites in U937 cells after BM-adipocyte co-culture and etomoxir treatment (S2); Genes whose expression was altered in U937 cells co-cultured with MSCs or BM-adipocytes and treated with etomoxir (S3); Genes whose expression was altered most often in U937 and THP1 cells by BM-adipocyte co-culture and treatment with etomoxir (S4); Proteins whose expression was altered in U937 cells by BM-adipocyte co-culture (S5).

Cobalt-free, nickel-rich positive electrode materials are attracting attention because of their high energy density and low cost, and the ultimate material is LiNiO

Anterior cervical disc replacement (ACDR) using cervical artificial disc (CAD) has the advantage of maintaining the range of motion (ROM) at the surgical level, subsequently reducing the postoperative risk of adjacent disc disease. Following the approval for the clinical use in Japan, a post-marketing surveillance (PMS) study was conducted for two different types of CAD, namely, Mobi-C (metal-on-plastic design) and Prestige LP (metal-on-metal design). The objective of this prospective observational multicenter study was to analyze the first 2-year surgical results of the PMS study of 1-level ACDR in Japan. A total of 54 patients were registered (Mobi-C, n = 24, MC group; Prestige LP, n = 30, PLP group). Preoperative neurological assessment revealed radiculopathy in 31 patients (57.4%) and myelopathy in 15 patients (27.8%). Preoperative radiological assessment classified the disease category as disc herniation in 15 patients (27.8%), osteophyte in 6 patients (11.1%), and both in 33 patients (61.1%). The postoperative follow-up rates at 6 weeks, 6 months, 1 year, and 2 years after ACDR were 92.6%, 87.0%, 83.3%, and 79.6%, respectively. In both groups, patients' neurological condition improved significantly after surgery. Radiographic assessment revealed loss of mobility at the surgical level in 9.5% of patients in the MC group and in 9.1% of patients in the PLP group. No secondary surgeries at the initial surgical level and no serious adverse events were observed in either group. The present results suggest that 1-level ACDR is safe, although medium- to long-term follow-up is mandatory to further verify the validity of ACDR for Japanese patients.

Background: The amyloid-β oligomers, consisting of 10–20 monomers (AβO10–20), have strong neurotoxicity and are associated with cognitive impairment in Alzheimer’s disease (AD). However, their role in patients with idiopathic normal pressure hydrocephalus (iNPH) is poorly understood. Objective: We hypothesized that cerebrospinal fluid (CSF) AβO10–20 accumulates in patients with iNPH, and its clearance after CSF shunting contributes to neurological improvement. We measured CSF AβO10–20 levels before and after CSF shunting in iNPH patients evaluating their diagnostic and prognostic role. Methods: We evaluated two iNPH cohorts: “evaluation” (cohort-1) with 32 patients and “validation” (cohort-2) with 13 patients. Comparison cohorts included: 27 neurologically healthy controls (HCs), and 16 AD, 15 Parkinson’s disease (PD), and 14 progressive supranuclear palsy (PSP) patients. We assessed for all cohorts CSF AβO10–20 levels and their comprehensive clinical data. iNPH cohort-1 pre-shunting data were compared with those of comparison cohorts, using cohort-2 for validation. Next, we compared cohort-1’s clinical and CSF data: 1) before and after CSF shunting, and 2) increased versus decreased AβO10–20 levels at baseline, 1 and 3 years after shunting. Results: Cohort-1 had higher CSF AβO10–20 levels than the HCs, PD, and PSP cohorts. This result was validated with data from cohort-2. CSF AβO10–20 levels differentiated cohort-1 from the PD and PSP groups, with an area under receiver operating characteristic curve of 0.94. AβO10–20 levels in cohort-1 decreased after CSF shunting. Patients with AβO10–20 decrease showed better cognitive outcome than those without. Conclusion: AβO10–20 accumulates in patients with iNPH and is eliminated by CSF shunting. AβO10–20 can be an applicable diagnostic and prognostic biomarker.

Intervertebral device subsidence is one of the complications of anterior cervical discectomy and fusion. The biomechanical properties of vertebral bony endplate may be related to device subsidence. The aim of this study is to measure the cervical endplate bone density distribution using a novel 3D measurement method. Eight human cadaver cervical spines were obtained and levels C3-C7 were dissected and CT scanned. Three-dimensional (3D) CT model was created with the same 3D coordinates of the original DICOM dataset. The regional strength and stiffness of the endplate were determined by indentation testing. The indentation points were recorded by a photograph and the location of the indentation points was projected to the 3D CT model. Three-dimensional coordinates of the indentation point was obtained in the 3D space determined by the DICOM dataset. The area underneath the indentation point was calculated by a trilinear interpolation method directly. Data in HU and correlations with the indentation strength and stiffness were analysed. A positive correlation was found between HU and strength (r = 0.52) and between HU and stiffness (r = 0.41). Overall, mechanical strength and stiffness and HU in the superior endplate of the caudal vertebra were lower than those in the inferior endplate of the cranial vertebra in the same intervertebral disc. The mechanical properties and the HU were found to be significantly correlated, which employed a novel 3D HU measurement method, thus demonstrating potential to predict cervical endplate failure risk in a clinical setting.

Purpose Since a case of hydrocephalus in humans considered to be caused by ciliary dysfunction was first reported by Greenstone et al. in 1984, numerous papers on the correlation between ciliary function and hydrocephalus have been published. Methods We reviewed the published literature on primary ciliary dyskinesia in humans causing hydrocephalus, focusing on articles specifically examining the relation between ciliary function and hydrocephalus and its treatment. In addition, the authors’ experience is briefly discussed. Results Full texts of 16 articles reporting cases of human hydrocephalus (including ventriculomegaly) due to defects in ependymal ciliary function or primary ciliary dyskinesia observed in clinical practice were extracted. In recent years, studies on animal models, especially employing knockout mice, have revealed genetic mutations that cause hydrocephalus via ciliary dysfunction. However, a few reports on the onset of hydrocephalus in human patients with primary ciliary dyskinesia have confirmed that the incidence of this condition was extremely low compared to that in animal models. Conclusion In humans, it is rare for hydrocephalus to develop solely because of abnormalities in the cilia, and it is highly likely that other factors are also involved along with ciliary dysfunction.

Background Individuals with Sturge-Weber syndrome (SWS) often expereince intractable epilepsy and cognitive decline. We hypothesized that the extent of the leptomeningeal capillary malformation (LCM) may correlate with the severity of neurological impairment due to SWS. We tested the hypothesis in a cross-sectional study of seizure severity and electroencephalographic (EEG) findings and a retrospective cohort study for surgical indications related to the extent of the LCM. Methods We enrolled 112 patients and classified them according to LCM distribution: (1) bilateral, (2) hemispheric, (3) multilobar, and (4) single lobe. Age at seizure onset, seizure semiology and frequency, and EEG findings were compared. Surgical indications were evaluated for each group by Fisher exact test, and predictors for surgery were evaluated by univariate and multivariate analyses. Therapeutic efficacy was evaluated by the SWS-Neurological Score (SWS-NS). Results The bilateral and hemispheric groups had early seizure onset (4.0 months old and 3.0 months old), frequent seizures (88.9% and 80.6% had more than one per month), focal-to-bilateral tonic-clonic seizures (88.9% and 74.2%), and status epilepticus (100% and 87.1%). The groups’ EEG findings did not differ substantially. Surgical indications were present in 77.8% of the bilateral, 88.1% of the hemispheric, and 46.8% of the multilobar groups. Seizure more than once per month was a predictor of surgical treatment. Seizure subscore improved postoperatively in the hemispheric and multilobar groups. Even after surgical treatment, the bilateral and hemispheric groups exhibited higher SWS-NSs than members of the other groups. Conclusion Our study demonstrated a strong association between extensive LCM and epilepsy severity. Surgical intervention improved seizure outcome in patients with SWS with large LCMs.

OBJECTIVEImproved outcomes in patients with subarachnoid hemorrhage (SAH) treated at high-volume centers have been reported. The authors sought to examine whether hospital case volume and comprehensive stroke center (CSC) capabilities affect outcomes in patients treated with clipping or coiling for SAH.METHODSThe authors conducted a nationwide retrospective cohort study in 27,490 SAH patients who underwent clipping or coiling in 621 institutions between 2010 and 2015 and whose data were collected from the Japanese nationwide J-ASPECT Diagnosis Procedure Combination database. The CSC capabilities of each hospital were assessed by use of a validated scoring system based on answers to a previously reported 25-item questionnaire (CSC score 1–25 points). Hospitals were classified into quartiles based on CSC scores and case volumes of clipping or coiling for SAH.RESULTSOverall, the absolute risk reductions associated with high versus low case volumes and high versus low CSC scores were relatively small. Nevertheless, in patients who underwent clipping, a high case volume (> 14 cases/yr) was significantly associated with reduced in-hospital mortality (Q1 as control, Q4 OR 0.71, 95% CI 0.55–0.90) but not with short-term poor outcome. In patients who underwent coiling, a high case volume (> 9 cases/yr) was associated with reduced in-hospital mortality (Q4 OR 0.69, 95% CI 0.53–0.90) and short-term poor outcomes (Q3 [> 5 cases/yr] OR 0.75, 95% CI 0.59–0.96 vs Q4 OR 0.65, 95% CI 0.51–0.82). A high CSC score (> 19 points) was significantly associated with reduced in-hospital mortality for clipping (OR 0.68, 95% CI 0.54–0.86) but not coiling treatment. There was no association between CSC capabilities and short-term poor outcomes.CONCLUSIONSThe effects of case volume and CSC capabilities on in-hospital mortality and short-term functional outcomes in SAH patients differed between patients undergoing clipping and those undergoing coiling. In the modern endovascular era, better outcomes of clipping may be achieved in facilities with high CSC capabilities.

The classification of spinal extradural arteriovenous fistulas (AVFs) was reported based on a case series treated by microsurgery in 2009 and endovascular interventions in 2011. The present report describes a patient with extradural AVFs at the cervical spine manifesting gradual progressive radiculomyelopathy of bilateral upper extremities. Magnetic resonance imaging (MRI) revealed a mass sign from C1 to C4 at the right ventral side and the spinal cord was deviated to the left and indicated as a flow void sign. Diagnostic angiography revealed an extradural AVFs located at the C1–C4 level that was supplied by bilateral radicular artery from the vertebral artery (VA) and right ascending cervical artery (ACA). The shunting points were recognized multiply at C2/3 and C3/4 levels on the right. The transvenous embolization to the enlarged extradural venous plexus around the shunting points via right hypoglossal canal and the transarterial embolization against multi-feeders of the branch of left radicular artery, right ACA achieved complete occlusion of the lesions. His symptom was gradually recovered, and angiography performed 2 weeks after embolization showed no recurrence. When the arteriovenous shunts in the upper cervical spine were high flow shunts, transvenous approach via the hypoglossal canal might be one option for the treatment of spinal extradural AVFs.

Spontaneous intracranial hypotension (SIH) is caused by cerebrospinal fluid (CSF) leakage. Patients with SIH experience postural headaches, nausea, etc., due to CSF hypovolemia. Imaging studies and clinical examinations, such as radioisotope (RI) scintigraphy, are useful for diagnosing SIH. However, 20-30% of patients do not show typical morphology and clinical test results. We previously reported that CSF contains transferrin (Tf) isoforms: “brain-type” Tf derived from the choroid plexus and “serum-type” Tf derived from blood. We showed that both isoforms increased in the CSF of patients with SIH by Western blotting. In the present study, we demonstrate that conventional ELISA for quantifying total Tf is useful for diagnosing SIH more accurately than Western blotting. In addition, SIH with chronic subdural hematoma (CSDH) was also accurately diagnosed. Total Tf in the CSF can serve as a useful biomarker for diagnosing SIH with or without CSDH.

Each year, the Japan Neurosurgical Society (JNS) reports up-to-date statistics from the Japan Neurosurgical Database regarding case volume, patient demographics, and in-hospital outcomes of the overall cohort and neurosurgical subgroup according to the major classifications of main diagnosis. We hereby report patient demographics, in-hospital mortality, length of hospital stay, purpose of admission, number of medical management, direct surgery, endovascular treatment, and radiosurgery of the patients based on the major classifications and/or main diagnosis registered in 2018 and 2019 in the overall cohort (523283 and 571143 patients, respectively) and neurosurgical subgroup (177184 and 191595 patients, respectively). The patient demographics, disease severity, proportion of purpose of admission (e.g., operation, 33.9-33.5%) and emergent admission (68.4-67.8%), and in-hospital mortality (e.g., cerebrovascular diseases, 6.3-6.5%; brain tumor, 3.1-3%; and neurotrauma, 4.3%) in the overall cohort were comparable between 2018 and 2019. In total, 207783 and 225217 neurosurgical procedures were performed in the neurosurgical subgroup in 2018 and 2019, respectively, of which endovascular treatment comprised 19.1% and 20.3%, respectively. Neurosurgical management of chronic subdural hematoma (19.4-18.9%) and cerebral aneurysm (15.4-14.8%) was most common. Notably, the proportion of management of ischemic stroke/transient ischemic attack, including recombinant tissue plasminogen activator infusion and endovascular acute reperfusion therapy, increased from 7.5% in 2018 to 8.8% in 2019. The JNS statistical update represents a critical resource for the lay public, policy makers, media professionals, neurosurgeons, healthcare administrators, researchers, health advocates, and others seeking the best available data on neurosurgical practice.

Objectives Comorbidities of idiopathic normal pressure hydrocephalus (iNPH), such as Alzheimer's disease (AD) and Parkinson's spectrum (PS) disorder, can affect the long-term prognosis of cerebrospinal fluid (CSF) shunting. Therefore, it is important to be able to predict comorbidities in the early stage of the disease. This study aimed to predict the comorbidities of iNPH using neuropsychological tests and cognitive performance evaluation. Materials & methods Forty-nine patients with possible iNPH were divided into three groups: iNPH without AD or PS comorbidity (group-1), iNPH with AD comorbidity (group-2), and iNPH with PS comorbidity (group-3), according to CSF biomarkers such as phosphorylated tau and dopamine transporter imaging. Scores on the new EU-iNPH-scale, which is based on 4 neuropsychological tests (Rey Auditory Verbal Learning Test, Grooved Pegboard test, Stroop colour-naming test and interference test), were compared for each group. In addition, the scores before and 12 months after CSF shunting for each group were compared. Results EU-iNPH-scale using 4 neuropsychological tests could distinguish group-1 from group-2 or group-3 by area under the curve values of 0.787 and 0.851, respectively. Patients in group-1 showed a remarkable increase in memory and learning ability after surgery. Group-2 performed significantly poorer than group-1 patients on memory testing, but otherwise showed improvements in most of the neuropsychological tests. Group-3 performed significantly worse than group-1 patients-especially on Stroop tests-but showed post-surgery improvement on only the Stroop colour-naming test. Conclusions The 4 neuropsychological tests of the EU-iNPH-scale can help predict iNPH comorbidities and evaluate the prognosis of CSF shunting.

Background and purpose The pathophysiology of idiopathic normal pressure hydrocephalus (iNPH) has not been completely clarified. We investigated the brain structure in iNPH using automatic ventricular volumetry, single-tensor diffusion tensor imaging (DTI) and bi-tensor free-water (FW) imaging analyses while focusing on cognitive impairments before and after lumboperitoneal shunt surgery. Materials and methods This retrospective study included 12 iNPH patients with structural magnetic resonance imaging (MRI) and diffusion MRI (dMRI) on a 3T-MRI scanner who underwent neuropsychological assessments before and after shunting and 8 healthy controls. Ventricular volumetry was conducted on structural MRI datasets using FreeSurfer. Ventricular volume was compared pre- and postoperatively. Correlation analyses were performed between ventricular volume or volume change and neuropsychological scores or score change. Tract-based spatial statistics were performed using dMRI datasets for group analyses between iNPH and controls and between pre- and post-surgery iNPH patients and for correlation analyses using neuropsychological scores. Tract-specific analyses were performed in the anterior thalamic radiation (ATR), followed by comparison and correlation analyses. Results The third ventricular volume was significantly decreased after shunting; its volume reduction negatively correlated with a neuropsychological improvement. Compared with controls, iNPH patients had lower fractional anisotropy and higher axial, radial, and mean diffusivities, and FW in the periventricular white matter including ATR, resulting in no difference in FW-corrected indices. Single-tensor DTI indices partially correlated with neuropsychological improvements, while FW-corrected indices had no correlations. Conclusion Third ventricle enlargement is possibly linked to cognitive impairment and FW imaging possibly provides better white matter characterization in iNPH.

Purpose: Despite extensive research, an effective and safe treatment for diffuse intrinsic pontine glioma (DIPG) has not been established. In this study, we investigate the therapeutic potential of combination therapy with histone deacetylase (HDAC) and carbonic anhydrase 9 (CA9) inhibitors against DIPG.Methods: We used RNA sequencing data from DIPG patient samples to evaluate the expression of the carbonic anhydrase family and the activity of the hypoxia signaling pathway. Next, we performed a synergy screen using CA9 inhibitor SLC-0111 and the HDAC inhibitors panobinostat, vorinostat, entinostat, and pyroxamide. We selected the SLC-0111/HDACi combination showing the highest synergy, and its effects on cell proliferation, invasion, and migration were evaluated. We also measured changes in histone acetylation, apoptosis, cell cycle, and intracellular pH.Results: CA9 was significantly upregulated in human DIPG samples. Furthermore, pathways downstream of CA9 were found to be activated when compared to normal brain tissue. The synergy screen revealed that the combination of SLC-0111 and pyroxamide was most effective at inhibiting DIPG cell proliferation. Furthermore, this combination reduced cell migration and invasion potential while enhancing histone acetylation with subsequent reduction of cell population in S Phase. Finally, the SLC-0111 and pyroxamide combination showed greater reduction of intracellular pH as compared to each agent alone.Conclusion: Our in vitro data suggest that the combination of SLC-0111 and pyroxamide shows promise in the treatment of experimental DIPG. Based on these findings, further investigation of this combination therapy in preclinical models is warranted.

ObjectivesTo examine the national, 6-year trends in in-hospital clinical outcomes of patients with subarachnoid haemorrhage (SAH) who underwent clipping or coiling and the prognostic influence of temporal trends in the Comprehensive Stroke Center (CSC) capabilities on patient outcomes in Japan.DesignRetrospective study.SettingSix hundred and thirty-one primary care institutions in Japan.ParticipantsForty-five thousand and eleven patients with SAH who were urgently hospitalised, identified using the J-ASPECT Diagnosis Procedure Combination database.Primary and secondary outcome measuresAnnual number of patients with SAH who remained untreated, or who received clipping or coiling, in-hospital mortality and poor functional outcomes (modified Rankin Scale: 3–6) at discharge. Each CSC was assessed using a validated scoring system (CSC score: 1–25 points).ResultsIn the overall cohort, in-hospital mortality decreased (year for trend, OR (95% CI): 0.97 (0.96 to 0.99)), while the proportion of poor functional outcomes remained unchanged (1.00 (0.98 to 1.02)). The proportion of patients who underwent clipping gradually decreased from 46.6% to 38.5%, while that of those who received coiling and those left untreated gradually increased from 16.9% to 22.6% and 35.4% to 38%, respectively. In-hospital mortality of coiled (0.94 (0.89 to 0.98)) and untreated (0.93 (0.90 to 0.96)) patients decreased, whereas that of clipped patients remained stable. CSC score improvement was associated with increased use of coiling (per 1-point increase, 1.14 (1.08 to 1.20)) but not with short-term patient outcomes regardless of treatment modality.ConclusionsThe 6-year trends indicated lower in-hospital mortality for patients with SAH (attributable to better outcomes), increased use of coiling and multidisciplinary care for untreated patients. Further increasing CSC capabilities may improve overall outcomes, mainly by increasing the use of coiling. Additional studies are necessary to determine the effect of confounders such as aneurysm complexity on outcomes of clipped patients in the modern endovascular era.

BackgroundCongenital hydrocephalus occurs with some inheritable characteristics, but the mechanisms of its development remain poorly understood. Animal models provide the opportunity to identify potential genetic causes in this condition. The Hydrocephalus-Texas (H-Tx) rat strain is one of the most studied animal models for investigating the causative genetic alterations and analyzing downstream pathogenetic mechanisms of congenital hydrocephalus.MethodsComparative genomic hybridization (CGH) array on non-hydrocephalic and hydrocephalic H-Tx rats was used to identify causative genes of hydrocephalus. Targeted gene knockout mice were generated by CRISPR/Cas9 to study the role of this gene in hydrocephalus. ResultsCGH array revealed a copy number loss in chromosome 16p16 region in hydrocephalic H-Tx rats, encompassing the Ptpn20 gene, without change in most non-hydrocephalic H-Tx rats. Ptpn20-knockout (Ptpn20-/-) mice were generated and found to develop ventriculomegaly. Furthermore, high expression of phosphorylated Na-K-Cl cotransporter 1 (pNKCC1) was identified in the choroid plexus (CP) epithelium of mice lacking Ptpn20. ConclusionsThe high level of pNKCC1 in CP epithelium may cause the overproduction of cerebrospinal fluid and contribute to the formation of hydrocephalus in Ptpn20-/- mice. Ptpn20 may be a potential therapeutic target in the treatment of hydrocephalus.

Background Congenital hydrocephalus occurs with some inheritable characteristics, but the mechanisms of its development remain poorly understood. Animal models provide the opportunity to identify potential genetic causes in this condition. The Hydrocephalus-Texas (H-Tx) rat strain is one of the most studied animal models for investigating the causative genetic alterations and analyzing downstream pathogenetic mechanisms of congenital hydrocephalus. Methods Comparative genomic hybridization (CGH) array on non-hydrocephalic and hydrocephalic H-Tx rats was used to identify causative genes of hydrocephalus. Targeted gene knockout mice were generated by CRISPR/Cas9 to study the role of this gene in hydrocephalus. Results CGH array revealed a copy number loss in chromosome 16p16 region in hydrocephalic H-Tx rats at 18 days gestation, encompassing the protein tyrosine phosphatase non-receptor type 20 (Ptpn20), a non-receptor tyrosine phosphatase, without change in most non-hydrocephalic H-Tx rats. Ptpn20-knockout (Ptpn20−/−) mice were generated and found to develop ventriculomegaly at 8 weeks. Furthermore, high expression of phosphorylated Na-K-Cl cotransporter 1 (pNKCC1) was identified in the choroid plexus (CP) epithelium of mice lacking Ptpn20 from 8 weeks until 72 weeks. Conclusions This study determined the chromosomal location of the hydrocephalus-associated Ptpn20 gene in hydrocephalic H-Tx rats. The high level of pNKCC1 mediated by Ptpn20 deletion in CP epithelium may cause overproduction of cerebrospinal fluid and contribute to the formation of hydrocephalus in Ptpn20−/− mice. Ptpn20 may be a potential therapeutic target in the treatment of hydrocephalus.

Clipping of paraclinoid aneurysm is still challenging because of poor visual morbidity. The extradural temporopolar approach was applied to clip paraclinoid aneurysms, with the expectation of reducing visual morbidity. Factors related to poor visual morbidity were evaluated, to assess the results for clipping of paraclinoid aneurysms.A series of 40 unruptured paraclinoid aneurysms in 38 patients were clipped via extradural temporopolar approach. Preoperative and postoperative states of visual cognitive function and radiological outcomes were investigated. Aneurysms were classified into dorsal type or non-dorsal type, and small (9 mm) or not-small (≥9 mm), respectively, to identify factors correlated with visual morbidity.Complete clipping rate was 90.0% without any recurrence (mean: 5.2 years). Visual morbidity was unexpectedly high at 28.9%, including 2.7% of blindness immediately after the operation, and 23.7% and 2.7% at the final examination (mean: 3.6 years). Multivariate analysis showed aneurysm size was significantly correlated with worse visual outcome. Visual morbidity was 13.3% and 11.1% for dorsal and the non-dorsal small aneurysms, respectively, and all these cases showed visual field defect limited to the nasal quadrant without decreased visual acuity. In contrast, the non-dorsal not-small aneurysms showed significantly worse visual morbidity (60%) with decreased visual acuity.Clipping via extradural temporopolar approach can achieve durable treatment for small unruptured paraclinoid aneurysms with acceptable visual morbidity. Visual morbidity of the not-small non-dorsal type, however, was poor. The indications for clipping of paraclinoid aneurysm should be limited to small aneurysms, especially the dorsal type in young patients.

Background Atlantoaxial transarticular screw fixation (TASF) is a procedure that involves inserting screws vertically into the articular processes of C1 and C2. However, this procedure is associated with a risk of injury to surrounding structures including the vertebral artery, carotid artery, pharynx, and spinal cord by misinserting K-wires or screws. This study was performed to evaluate the risk of TASF using 3-dimensional navigation-guided drilling and screw insertion tract creation. Methods Three patients underwent the surgical procedure using a navigation system guided by intraoperative computed tomography. The insertion tract of the screw was created using the navigation system to avoid penetration of the C1 anterior arch or damage to the vertebral artery. A blunt-tipped guide wire was used, which was safe to advance to the cortex of the anterior arch of C1. Results There were no complications or instrument failures in any of the surgeries. In each case, the total radiation dose delivered was 5.31–7.02 mGy, and total radiation exposure time was 55.6–106.8 seconds. Bone fusion was achieved in all cases. Conclusions TASF using a navigation system for drilling is useful for accurate placement of K-wire and preventing damage of the vital structures, lowering the risk of the procedure.

There have recently been reports of patients who developed postprocedural symptoms or alterations due to delayed foreign body embolisms observed in imaging findings. Polymer coating of devices have been described as a possible cause of foreign body embolisms, manifesting in delayed granulomatous responses and exhibiting characteristic imaging findings. In four of 4,025 patients who underwent coil embolization in our hospital or its affiliated facilities, similar findings were observed. Delayed lesions appeared between 1 month and 1 year after the procedures. There was extensive edema in the perfusion area of the treated vessels. In two cases examined by contrast-enhanced magnetic resonance imaging, multiple solid enhancing lesions within vasogenic edema were observed. Biopsy revealed a membranous foreign body in a blood vessel with surrounding foreign body granuloma formation in 1 case. Because these findings are similar to those of cases reported previously, they were considered as a foreign body embolism due to coating separations from the devices. Polymer coating separation occurs most frequently from guidewires. Especially if a metal introducer is used, the risk of separation increases. Surgeons should carefully follow the manufacturers’ instructions when they use these devices and should acknowledge and report any events that may occur. Although these complications are extremely rare, further studies are warranted of similar cases; and we should prepare and share information on these intravascular devices for wide-scale dissemination in the industry.

Quantitative magnetic resonance imaging (MRI) with multislice, multi-echo, and multi-delay acquisition enables simultaneous quantification of R1 and R2 relaxation rates, proton density, and the B1 field in a single acquisition, and requires only about 6 minutes for full-head coverage. Using dedicated SyMRI software, radiologists can generate any contrast-weighted image by manipulating the acquisition parameters, including repetition time, echo time, and inversion time. Moreover, automatic brain tissue segmentation, volumetry, and myelin measurement can also be performed. Using the SyMRI approach, a shorter scan time, an objective examination, and personalized MR imaging parameters can be obtained in daily clinical pediatric imaging. Here we summarize and review the use of SyMRI in imaging of the pediatric brain, including the basic principles of MR quantification along with its features, clinical applications, and limitations.

Early-stage glioblastoma has few identifiable findings; clinical significance of its early diagnosis and treatment remains unclear as no report has described treatment and long-term follow-up for early-stage glioblastoma. Here, we report a case of a 69-year-old woman with early-stage glioblastoma treated by microsurgical resection and chemoradiotherapy. Magnetic resonance imaging (MRI) revealed a small high-intensity lesion in the right temporal lobe on T2-weighted imaging. Contrast-enhanced T1-weighted MRI revealed ring enhancement. On magnetic resonance spectroscopy, the lesion demonstrated increased choline and reduced N-acetyl-aspartate levels compared with the normal brain. Positron emission tomography with 11C-methionine (MET) revealed 11C-methionine uptake in the lesion. Microsurgical resection was performed, and glioblastoma was pathologically diagnosed. The patient was treated with local radiotherapy and temozolomide chemotherapy postoperatively. Eight years postoperatively, the patient is surviving without tumor recurrence, but progressive cognitive impairment developed 6 years' postoperatively. Aggressive treatment of early-stage glioblastoma may improve its extremely poor prognosis. Conversely, cognitive impairment may become a significant medical and social problem when effective therapies for glioblastoma are developed.

Stent-assisted coiling is recognized as effective to induce progressive occlusion and prevent recurrence of aneurysm. The long-term effects of stent-assisted coiling of sidewall-type and terminal-type aneurysms were comparatively analyzed focusing on the different hemodynamic characteristics.Retrospective analysis included a total of 120 unruptured aneurysms in 116 consecutive patients who underwent stent-assisted coiling and completed 2-year follow-up. The stent systems, baseline characteristics, and postcoiling occlusion status of sidewall-type and terminal-type aneurysms were assessed.Sidewall-type aneurysms had a significantly larger dome size (P = 0.02) and greater diameter of the parent vessel (P0.001) than terminal-type aneurysms. Initial occlusion status of the aneurysms was significantly maintained for 2 years in both sidewall-type and terminal-type aneurysms as follows: sidewall-type aneurysms showed that complete occlusion (CO), neck remnants (NRs), and body filling (BF) immediately posttreatment were significantly correlated with CO (P0.05), NRs (P 0.01), and BF (P0.05) at 2-year follow-up, respectively, and terminal-type aneurysms showed that CO, NRs, and BF immediately posttreatment were significantly correlated with CO (P0.05), NRs (P0.05), and BF (P 0.05) at 2-year follow-up, respectively. In addition, sidewall-type aneurysms with CO immediately posttreatment were significantly correlated with non-NRs (P0.01) and non-BF (P 0.01) at 2-year follow-up.Stent-assisted coiling allows higher coil packing for sidewall-type aneurysms, but the indication should be carefully considered for terminal-type aneurysms.

Glioblastoma (GBM) is pathologically characterized by highly malignant neoplastic cells, focal necrosis and aberrant blood vessels composed of disorganized endothelial cells and pericytes. The recent cancer microarray database revealed upregulation of fibulin-7 (Fbln7), a member of the fibulin family, but provided no information on the tissue localization or biological function. In the present study, we demonstrated that Fbln7 is markedly overexpressed by the GBM tissue among astrocytic tumors, and immunolocalized mainly to endothelial cells and pericytes of the glomeruloid and hypertrophied microvessels. The production of Fbln7 by endothelial cells and pericytes was confirmed in cultured human umbilical vein endothelial cells (HUVEC) and human brain vascular pericytes (HBVP) and vascular endothelial growth factor (VEGF) stimulated the Fbln7 expression in HUVEC. Fbln7 bound to angiopoietin-1, but not angiopoietin-2 or Tie2 receptor, through interaction between the N-terminal portions of Fbln7 and angiopoietin-1, and it blocked phosphorylation of Tie2 receptor in HUVEC. In a coculture assay using HUVEC and HBVP, multilayered and irregular-shaped tube-like structures of HUVEC were induced by treatment with a high concentration of VEGF. This was accompanied by Fbln7 overproduction by HUVEC and angiopoietin-1 expression by HBVP. The production of aberrant VEGF-induced tube-like structures was attenuated by treatment with antibody or synthetic peptides specific to the Fbln7 N-terminal domain or knockdown of Fbln7. These data demonstrate that Fbln7 is overexpressed by endothelial cells and pericytes of the abnormal microvessels in GBM, and suggest that Fbln7 may contribute to the aberrant vessel formation by modulation of the angiopoietin-1/angiopoietin-2-Tie2 axis.

Background Patients with idiopathic normal-pressure hydrocephalus (iNPH) are typically older adults with multiple comorbidities that are associated with a reduction in the efficacy of iNPH treatment via cerebrospinal fluid (CSF) shunt placement. Objective The present study aimed to investigate the effectiveness of CSF shunt for iNPH using data from a nationwide epidemiological survey in Japan. Methods We examined 1,423 patients (581 women) aged ≥60 years (median age [25%-75%]: 77 [73-80] years) who were diagnosed with iNPH following a hospital visit in 2012. Patients who experienced an improvement of at least one modified Rankin Scale (mRS) grade after the CSF shunt were classified as "improvement" while the remaining patients were classified as "non-improvement." The efficacy of the shunt intervention (n = 842) was analyzed using a binomial logistic regression analysis. Results An analysis of risk factors associated with shunt placement in patients with mRS grade 2 revealed an association between comorbid chronic ischemic lesions (odds ratio [OR], 2.28; 95% confidence interval [CI], 1.11-4.67; p = 0.025) and cervical spondylosis (OR, 3.62; 95% CI, 1.15-11.34; p = 0.027). Patients with mRS grade 3 at study entry had an association with comorbid Alzheimer's disease (OR, 3.02; 95% CI, 1.44-6.31; p = 0.003). Conclusions The results presented here showed that any age-related risk is minimal and should not be cause for rejection of surgical treatment options. Clinical decisions regarding CSF shunt should be individualized to each patient, with adequate consideration of the relative risks and benefits, including maximizing a healthy life expectancy.

Lithium iron phosphate (LiFePO4) is known to undergo a two-phase coexistence reaction during charging and discharging, and this phase transition is reported to be the rate-determining step of the cell reaction (1). Such a phase transition involves not only the rearrangement of the LiFePO4/FePO4 border but also the charge transfer process at the electrode/electrolyte interface, but the detail has been so far unknown. If the rearrangement of the solid border is truly the rate-determining step, it is expected that the phase transition behavior is not affected by the type of electrolyte used for the cell. In this study, we compare the activation energy of the phase transition reaction of LiFePO4 using the potential step measurements in non-aqueous and aqueous electrolyte cells to clarify the effect of the charge transfer at the electrode/electrolyte interface. The LiFePO4 powder (Hosen) was mixed with carbon black (Denka) and polyvinylidene fluoride (Kureha) in a weight ratio of 85:10:5 with 1-methyl-2-pyrrolidone (KANTO CHEMICAL, 99%). The slurry was coated onto a titanium current collector and dried at 80°C. A non-aqueous-type three-electrode cell composed of the LiFePO4 as a working electrode, lithium foils as a counter and reference electrodes, and a 1 mol dm–3 solution of LiPF6 in ethylene carbonate and diethyl carbonate (1:1 v/v) as an electrolyte solution was constructed in an Ar-filled glove box. An aqueous-type three-electrode cell was composed of the LiFePO4 as a working electrode, a Ni wire as a counter electrode, Ag/AgCl/sat’d KClaq as a reference electrode, and a 0.5 mol dm–3 Li2SO4 aqueous solution as an electrolyte solution. The charging–discharging behavior was firstly measured to confirm the cell characteristics and then the potential step measurement was employed. The Avrami plots based on the potential step results (2) were used to obtain the reaction rate constant k. These electrochemical measurements were performed at the chosen temperature. Then we calculated the activation energy of kusing the Arrhenius plot. The electrochemical measurements were performed in a constant temperature oven. Figure 1 (a) shows the transient current behavior for the cell with the aqueous electrolyte measured during the potential step from open circuit potential to 0.4 V, where LiFePO4 is completely converted into FePO4. Figure 1 (b) shows the Avlami plot (2), where f corresponds to the volume fraction of the converted FePO4, calculated from the accumulated current values. The slope was nearly unity, indicating that the system follows the first-order reaction kinetics f = 1-exp(-kt), as well as the case for the non-aqueous electrolytes. Then, we calculated the activation energy using the Arrhenius plot in the aqueous electrolyte and the non-aqueous electrolyte. The activation energy of the aqueous electrolyte was smaller than that of the non-aqueous electrolyte, suggesting the effect of the electrode/electrolyte interface on the phase transition behavior. References (1) C. Fongy, A.-C. Gaillot, S. Jouanneau, D.Guyomard, and B. Lestriez, J. Electrochem. Soc., 157, A885-A891 (2010). (2) J. Allen, T.R. Jow, and J. Wolfenstine, Chem. Mater., 19, 2108-2011 (2007). (3) Y. Orikasa, T. Maeda, Y. Koyama, T. Minato, H. Murayama, K. Fukuda, H. Tanida, H. Arai, E. Matsubara, Y. Uchimoto, and Z. Ogumi, J. Electrochem. Soc. 160, A3061-A3065 (2013). Figure 1

Metal-air secondary batteries using alkaline electrolyte solutions are promising candidates for next-generation large-scale energy storage systems because of their potential high capacity, low cost, and high safety standard. However, large overpotential of bifunctional air electrodes hindered their wide applications. Recently, increasing research on electrocatalysts for oxygen reduction reaction (ORR) and oxygen reduction reaction (OER) has been conducted to reduce the overpotential, and many active catalysts have been developed. On the other hand, formation of reaction sites is also important since the reaction sites for ORR and OER are basically different1. In this work, we investigated the reaction sites in porous gas diffusion electrodes (GDE) and constructed a GDE with a double-layered catalyst layer based on the difference in the reaction sites for ORR and OER2. La0.6Ca0.4CoO3 (LCCO, bifunctional catalyst), La0.4Sr0.6MnO3 (LSMO, ORR catalyst) and Ca2FeCoO5 (CFCO, OER catalyst) were synthesized by the polymerized complex method. Porous gas diffusion electrodes are constructed by the hot-press method. Catalyst layers were composed of the prepared catalyst (50 wt%), graphitized carbon black (35 wt%), and poly(tetrafluoroethylene) (15 wt%). Gas diffusion layers (GDL) were commercial carbon papers (TGP-H-030H, Chemix). IR-corrected polarization curves were measured by the constant current and AC impedance measurements. Oxygen diffusion resistances for ORR and OER were estimated from the difference in the steady-state potential between pure oxygen and air atmosphere (⊿E = |E O2 – Eair|). Larger increase in ⊿E indicates larger oxygen diffusion resistances in the oxygen reaction processes3. Figure 1 (a, b) shows ⊿E-I curves of LCCO-GDE for ORR and OER in 4.0 and 8.0 dm–3 KOHaq. The oxygen permeability(D O2×C O2) in 4.0 dm–3 KOHaq is 16 times as large as that in 8.0 dm–3 KOHaq while the ion conductivities of these electrolyte solutions are at the same extent. The increase in ⊿E for ORR was larger in 8.0 dm–3 KOHaq, indicating dissolved oxygen involved in the ORR process. In contrast, the ⊿E for OER was nearly negligible in these electrolyte solutions, suggesting that oxygen was mainly transported as bubbles. We also measured ⊿E-I curves of the LCCO-GDE in 8.0 dm–3 KOHaq having different catalyst layer thicknesses. The increases in ⊿E were almost independent of the catalyst layer thicknesses for ORR and OER, suggesting that the reaction sites were concentrated in the catalyst layer. Finally, we compared polarization curves of the GDEs with single-layered catalyst layer (LSMO+CFCO|DGL-GDE) and double-layered catalyst layers (LSMO|CFCO|GDL-GDE and CFCO|LSMO|GDL-GDE) to identify the reaction sites for ORR and OER (Fig. 1 (c, d)). The smallest overpotential of CFCO|LSMO|GDL-GDE for both ORR and OER showed that the reaction sites for ORR and OER were concentrated at the electrolyte-side and gas-side, respectively. In addition, CFCO|LSMO|GDL-GDE showed higher durability than LSMO+CFCO|DGL-GDE. From these results, it can be concluded that the placement of the ORR and OER catalysts on the electrolyte-side and gas-side of the CL can improve both activity and durability of the bifunctional air electrode. References [1] A. Ikezawa, K. Miyazaki, T. Fukutsuka, T. Abe, Electrochem. Commun., 84, 53-56 (2017). [2] A. Ikezawa, K. Seki and H. Arai, Electrochim. Acta, 394, 139128 (2021). [3] A. Kaisheva, I. Iliev, S. Gamburzev, J. Power Sources, 13, 181-195 (1984). Figure 1

To determine whether increasing thrombectomy-capable hospitals with moderate comprehensive stroke center (CSC) capabilities is a valid alternative to centralization of those with high CSC capabilities. This retrospective, nationwide, observational study used data from the J-ASPECT database linked to national emergency medical service (EMS) records, captured during 2013–2016. We compared the influence of mechanical thrombectomy (MT) use, the CSC score, and the total EMS response time on the modified Rankin Scale score at discharge among patients with acute ischemic stroke transported by ambulance, in phases I (2013–2014, 1461 patients) and II (2015–2016, 3259 patients). We used ordinal logistic regression analyses to analyze outcomes. From phase I to II, MTs increased from 2.7 to 5.5%, and full-time endovascular physicians per hospital decreased. The CSC score and EMS response time remained unchanged. In phase I, higher CSC scores were associated with better outcomes (1-point increase, odds ratio [95% confidence interval]: 0.951 [0.915–0.989]) and longer EMS response time was associated with worse outcomes (1-min increase, 1.007 [1.001–1.013]). In phase II, neither influenced the outcomes. During the transitional shortage of thrombectomy-capable hospitals, increasing hospitals with moderate CSC scores may increase nationwide access to MT, improving outcomes.

Lateral wall paraclinoid aneurysms (LPA) are a rare type of aneurysm located on the lesser curve side of the internal carotid artery (ICA) bend, at the level of the anterior clinoid process. The objective of this study was to assess the influence of flexion of the ICA on the morphology of aneurysms and outcome of endovascular treatment. Between 2003 and 2018, we treated 643 cases of unruptured paraclinoid aneurysms with endovascular therapy in our institution. Of those cases, aneurysms projecting laterally on preoperative angiography were defined as LPA. The degree of bending of the ICA (ICA angle) was measured and statistically analyzed in relation to the aneurysm characteristics and the occlusion status after treatment. In all, 43 aneurysms were identified. ICA angle was positively correlated with the maximum dome size of the aneurysm (P

Parkinson's disease(PD)is a degenerative disorder of the central nervous system. Its cardinal features are resting tremor, rigidity, bradykinesia, and postural instability. Several years after disease onset, many patients with PD exhibit postural deformities, including camptocormia, Pisa syndrome, and dropped head syndrome, which can lead to spinal deformities. In addition, spinal degenerative disorders are frequently associated with PD and can further impact the patients' quality of life. Current evidence suggests a multifactorial etiology for postural deformities and spinal degenerative disorders in PD, which includes abnormal stress on the spine(biomechanical factors), postural instability and impairment of postural compensation(physiological factors), and imbalance of dopaminergic signals(pharmacological factors). The relative contribution of these factors varies between patients and across symptoms. Consequently, neurologists have difficulty treating these axial problems. Moreover, many studies have reported poor outcomes and high complication rates of spinal surgery in patients with PD, which embarrasses spinal surgeons. An improved understanding of the mechanisms underlying spinal problems in PD might ultimately lead to more effective management of these disabling complications.

A metal-air battery is an electrochemical cell that has a metal negative electrode, an air positive electrode, and an electrolyte. The use of oxygen as an active material is beneficial in fabricating high energy battery, material availability, and battery cost. The negative materials are generally base metals such as lithium, aluminum, and zinc. Primary MABs can be classified into normal (ready-to-use) and reserve batteries whereas secondary MABs can be categorized into electrically rechargeable and mechanically rechargeable types. The choice of the negative metal chiefly determines the kind of electrolyte (e.g., aqueous or nonaqueous) and air electrode design (e.g., film or porous mass). Since the air electrode is semi-opened, the lifetime of the MABs is affected by the environment conditions such as humidity and temperature. Subsystems are applied to complement the functions of the cell components, including an auxiliary fan and a water management system.

Ependymoma is the most common primary intramedullary tumor of the spinal cord, accounting for a quarter of these tumors. We experienced a case of 'ependymoma of the spinal cord with a cystic lesion that presented as an intradural extramedullary tumor extending from the thoracic to lumbar vertebrae. In review of past literature on reports of spinal intradural extramedullary ependymoma, lesions spanning three or more vertebrae with cystic lesions were frequent, and about half were World Health Organization grade II or higher. Dissemination or recurrence of these tumors may occur after surgery. There is no consensus on postoperative adjuvant therapy for intradural extramedullary spinal ependymoma, but careful consideration should be given to the intraoperative findings and the characteristics of the tumor.

Purpose Antiplatelet therapy initiated before flow diverter placement is effective for the prevention of ischemic complications. However, the effectiveness of oral anticoagulant treatment is unclear. This retrospective study evaluated the complications and obliteration rates after flow diverter placement in patients taking anticoagulants. Methods A total of 155 cases were treated by Pipeline Flex placement for unruptured large and giant cerebral aneurysms in our hospital between October 2015 and June 2019. The groups of 8 patients taking anticoagulants before operation and 147 patients not taking anticoagulants were compared. Results Clopidogrel oral dose ( P = 0.002) was significantly lower in the anticoagulant group. Delayed aneurysm rupture ( P = 0.002) and additional treatment ( P = 0.009) rates were significantly higher and complete obliteration rate ( P = 0.011) was lower in the anticoagulant group. Conclusions Additional oral anticoagulant administration before flow diverter placement does not reduce ischemic complications compared to dual antiplatelet therapy, but does increase hemorrhagic complications, especially delayed aneurysm rupture. Complete obliteration of the cerebral aneurysm is difficult to achieve in patients taking anticoagulants.

Introduction Our previous community-based study demonstrated that some individuals with AVIM [asymptomatic ventriculomegaly with features of idiopathic normal pressure hydrocephalus (iNPH) on magnetic resonance imaging (MRI)] progressed to iNPH in several years. In this hospital-based study, we investigated the progression rate from AVIM to iNPH and its possible predictors. Methods We conducted a prospective study of participants with AVIM from several medical institutions/hospitals in Japan. AVIM is defined as “asymptomatic ventriculomegaly with features of iNPH on MRI”; in the present study, asymptomatic was defined as “0 (no symptoms) or 1 (presence of only subjective, but not objective, symptoms) on the iNPH Grading Scale (iNPH-GS).” We also measured possible predicting factors for AVIM-to-iNPH progression, including age, sex, body weight, blood pressure, diabetes mellitus, dyslipidemia, history of mental disease/head injury/sinusitis/smoking/alcohol-intake, Evans index, and the presence of DESH (disproportionately enlarged subarachnoid-space hydrocephalus) findings on brain MRI, and analyzed these potential predictive values. Results In 2012, 93 participants with AVIM were registered and enrolled in the study. Of these, 52 participants were able to be tracked for three years (until 2015). Of the 52 participants, 27 (52%) developed iNPH during the follow-up period (11 definite, 6 probable, and 10 possible iNPH), whereas 25 participants remained asymptomatic in 2015. Among the possible predictive factors examined, the baseline scores of iNPH-GS predicted the AVIM-to-iNPH progression. Conclusions The multicenter prospective study demonstrated that the progression rate from AVIM to iNPH was ~17% per year, and the baseline scores of iNPH-GS predicted the AVIM-to-iNPH progression.

The effectiveness and safety of intraoperative magnetic resonance imaging (iMRI) are evident from many reports over the past decade. However, these reports have mainly concerned surgeries for glioma and other intra-axial tumours, and applications of this approach for extra-axial tumours are poorly documented. We retrospectively examined three cases in which iMRI was used to assist in the removal of epidermoid cysts. T2-weighted images and diffusion-weighted images were acquired during the surgeries. The value to surgeons of images generated by iMRI, the length of interruption of surgery, and the safety of the patients were assessed. In this study, the images obtained through iMRI provided were clear representations of remnant tumours, even with a low-field system (0.4 Tesla). These images generated enough information to help surgeons decide whether to use an assistance device, such as an endoscope, to remove remnant tumours and whether further retraction of the brain was safe for patients and useful in tumour removal. Intraoperative MRI has long been thought unnecessary for surgery for tumours that are well demarcated and clearly visible under a surgical microscope; in this study, however, intraoperative MRI proved to be useful and safe for patients undergoing epidermoid cyst resection.

Background The amyloid-beta (Aβ) oligomer has strong neurotoxicity and is associated with cognitive impairment in Alzheimer’s disease (AD). However, its role in patients with idiopathic normal pressure hydrocephalus (iNPH) is poorly understood. We hypothesised that cerebrospinal fluid (CSF) stagnation leads to Aβ oligomer accumulation in patients with iNPH. We measured CSF Aβ oligomer levels before and after CSF shunting in patients with iNPH. Methods We evaluated two iNPH cohorts: an analysis cohort (cohort-1) with 52 patients and a validation cohort (cohort-2) with 13 patients. For comparison cohorts, we recruited 27 neurologically normal controls (NCs), 16 patients with AD, 15 patients with Parkinson’s disease (PD), and 14 patients with progressive supranuclear palsy (PSP). We measured CSF Aβ oligomer levels and assessed participants’ neurological statuses. We then compared the iNPH cohorts’ pre-shunting measurements with the comparison groups’ measurements and compared cohort-1’s measurements recorded before and after CSF shunting. Results iNPH cohort-1 had higher CSF Aβ oligomer levels than the NC, PD, and PSP cohorts. This result was validated with data from iNPH cohort-2. CSF Aβ oligomer levels differentiated iNPH cohort-1 from the PD and PSP groups, with an area under receiver operating characteristic curve of 0.94. Aβ oligomer levels in iNPH cohort-1 decreased after CSF shunting. However, there was no correlation between Aβ oligomer levels and cognitive functions in iNPH cohort-1. Conclusion The Aβ oligomer accumulates in patients with iNPH patients but can be eliminated with CSF shunting, suggesting that CSF stagnation causes Aβ oligomer accumulation in iNPH.

Pioglitazone (PGZ), a PPARγ agonist, has been used for diabetic patients as an insulin-sensitizing agent. Recent studies have demonstrated that PGZ increases adiponectin (APN) levels and provides vascular protection in ischemic conditions. This study was designed to assess the neuroprotective effects of PGZ against cerebral ischemia-reperfusion injury via an APN-related mechanism. Type 2 diabetic leptin-deficient mice (db/db) were administered PGZ for 1 week, and plasma insulin and APN levels were measured. These mice received a middle cerebral artery occlusion and reperfusion injury, and they were evaluated for the infarct volume and by immunohistochemistry and western blotting analysis at several time points after ischemia. PGZ-administered db/db mice showed improved insulin sensitivity, and the hemorrhagic rate and infarct volume were decreased (P < 0.05). In the PGZ-administered group, plasma APN levels increased compared with the vehicle group. In the db/db group, PGZ administration significantly suppressed inflammatory reactions and oxidative stress after reperfusion (P < 0.05). PGZ may be applicable for acute cerebral ischemia treatment in metabolic syndrome patients as well as antidiabetic agents.